At an incidence of 0.5 to 1.0 per 1000 births, cystic fibrosis (CF) is one of the most common fatal genetic disorders. Fortunately, its debilitating complications are sometimes avoided by early application of prophylactic and therapeutic measures, making early detection of CF important.
There is a close correlation between excessive concentrations of chloride (Cl.sup.-) and sodium (Na.sup.+) in sweat and the presence of the clinical syndrome. Typically, sweat chloride values in CF patients exceed 60 mmol/L, whereas non-CF subjects ordinarily have sweat chloride values of less than 40 mmol/L.
The "sweat test" is considered the definitive laboratory test for the diagnosis of CF. The three steps involved in all sweat testing are stimulation of sweating, collection of sweat, and measurement of its salt content. The Gibson-Cooke sweat test (GCST), which provides a quantitative measure of chloride concentration in sweat, has been approved by the Cystic Fibrosis Foundation as the most definitive sweat test. However, it requires specifically prescribed procedures for each step, a high level of quality control, dedicated technicians, and frequent performance to maintain high diagnostic efficiency. Another CF detection system utilizes a disposable chloride-sensor patch to screen for CF, permitting a qualitative diagnosis of "normal", "possible CF", or "classic CF" by comparing sample concentrations of chloride with a predetermined chloride concentration level (Lattin et al., U.S. Pat. No. 4,457,748, issued Jul. 3, 1984; Fogt et al., U.S. Pat. No. 4,846,182, issued Jul. 11, 1989; Fogt et al., U.S. Pat. No. 4,444,193, issued Apr. 24, 1984; W. Yeung, M.D., et al., Clin. Pediatrics, 23, 603-607 (1984); W. Varwick et al., Clin. Chem. 32, 850-853 (1986)). The indicator patch must be carefully monitored so that it is neither underfilled or overfilled. Digitized measurement of the precipitation area in a filled 20-mg patch has been used to derive a mathematical relationship between the area of chloride precipitation and the chloride concentration of standard NaCl solutions (W. Warwick et al., Clin. Chem., 36, 96-98 (1990)).
Sweat test CF indicator systems that are simple to use but that yield quantitative determinations of chloride concentrations are thus desirable. A test device that is capable of generating accurate chloride determinations from small sample sizes is particularly desirable because of the difficulty of obtaining large sweat samples from very young subjects.